Jasper Therapeutics’ monoclonal antibody briquilimab is effective at preventing mast-cell induced anaphylaxis and asthma in mice, new data suggest.
In an oral presentation and two posters at the annual meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI), which began Feb. 23, Jasper’s researchers described experiments showing that briquilimab depletes mast cells that lead to severe allergic reactions in mice with mast cell disorders, asthma caused by allergies and drug-induced allergic reactions.
The findings point to new directions for the drug, which is currently being tested for its ability to prevent hives, formally known as urticaria.
“While our initial development efforts with subcutaneous briquilimab have focused on urticaria and other dermatological conditions, we are excited by its broad potential in a variety of mast cell driven diseases,” Edwin Tucker, M.D., chief medical officer at Jasper, said in a press release. “The preclinical data being generated by our research team across numerous mast cell driven diseases is critical to determining the next indication for briquilimab clinical development this year.”
Mast cells are a type of white blood cell that’s found throughout the body. At normal levels, they help the immune system respond to pathogens and regulate other types of immune responses. But too much mast cell activation or too many mast cells can cause allergic reactions, chronic urticaria, asthma and a range of other problems.
Briquilimab works by blocking the signaling of an enzyme called c-Kit on mast cells. C-kit protects mast cells from undergoing processes that lead to apoptosis, or cell death. Early studies of briquilimab on healthy people showed that a subcutaneous injection was enough to deplete mast cells in the skin for up to three months.
The preclinical data shared in the oral presentation at the AAAAI meeting showed that briquilimab was effective both for prophylaxis and as a treatment for asthma in mouse models. In one set of experiments, mice that were sensitized to cockroach allergen—a known asthma trigger in humans—were treated with briquilimab 19 days before being exposed to the allergen. The treatment prevented the mice from developing inflammation in their airways, and the ones that received the drug had lower numbers of mast cells in their lungs and the skin of their backs.
In a second set of experiments, the same type of asthma mouse model developed a reaction to the allergen, was treated with briquilimab, then was exposed to the allergen again three days later. The drug again decreased airway inflammation and the number of mast cells in the lung and the skin of the animals’ backs. They also had better lung function than untreated mice.
In the poster presentations, the researchers showed that a single dose of briquilimab protected mice from mast-cell induced passive systemic anaphylaxis—a disease model of anaphylaxis where mice are sensitized to an allergen and subsequently exposed to it—as well as anaphylaxis due to drug allergies. Only one dose was required for protection.
Jasper expects initial data from a phase 1 study on briquilimab in chronic spontaneous urticaria, a mast cell disease that causes a skin rash, in mid-2024, according to a corporate presentation given Feb. 1. The company plans to launch a second phase 1 trial on the drug in chronic inducible urticaria, another form of the disease, in the first quarter of 2024, with data in the second half of the year.